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<p>The targeted delivery of anticancer chimeric proteins as a therapeutic agent improves drug effectiveness. Research has concentrated on developing novel treatments by exploiting the properties of cytokines, notably interleukins, to suppress the proliferation of cancerous cells. IL-37 is a cytokine that has anti-inflammatory properties, and it limits the development of hepatocellular carcinoma by impeding cell growth, invasion, and angiogenesis of tumor cells as well as strengthening the body’s immune defenses against cancer while Bombinin (BO1) is a peptide that shows anti-HCC activity by disrupting cell-cycle regulation and inducing apoptosis in liver cancer cells with minimal effects on normal hepatocytes. This study computationally designed a fusion protein IL 37-BO1 by combining the targeting IL-37 with the anti-cancer peptide BO1 via a rigid linker to focus treatment directly on cancerous cells. The secondary structure, tertiary structure, and the physiochemical properties of the engineered fusion protein IL 37-BO1 were estimated through GOR IV, trRosetta, and ProtParam respectively. Validation of protein quality and 3D structure was confirmed using ProSa-web, ERRAT2 and RAMPAGE servers. Next, the IL-37–BO1 fusion protein was docked with the IL18Rα–IL1R8 heterodimer receptor to evaluate its binding characteristics. The docked complex was subsequently analyzed for intermolecular interactions and subjected to molecular dynamics simulation to further investigate its structural stability and dynamic behavior. In-silico study showed that the newly designed possesses a basic composition and a molecular weight of 24&#xa0;kDa. The ERRAT value of 97.52% and 92.50% of the residues located within the most favorable region were predicted based on SAVES 6.0 analysis, ensuring structural stability. Finally, docking, molecular dynamics simulation, and interaction studies were carried out through ClusPro 2.0, GROMACS and PDBsum and PDBePISA which revealed 20 notable hydrogen bonds and 6 salt bridges, validating the stabilization of the docked complex. Docking and binding affinity analyses revealed a stable interaction, with an MM/GBSA score of − 106.26&#xa0;kcal/mol and a PRODIGY-predicted binding affinity (ΔG) of − 15.3&#xa0;kcal/mol. SoluProt also predicted a high expression potential of the fusion protein in E. coli with a score of 0.903. The results indicate that the IL-37-BO1 fusion protein can be expressed effectively in <i>E. coli</i> with high stability and activity. The engineered protein demonstrated reliable performance, effective molecular interaction, and high quality. Overall, the results support IL-37–BO1 as a promising and safe candidate for targeted cancer therapy.</p>

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Computational modeling, docking, and molecular dynamics analysis of IL-37–bombinin fusion protein targeting hepatocellular carcinoma

  • 期刊论文

  • 发表日期：

    2026年8月4日

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  • Ayesha Amin,
  • Hafiz Muhammad Rehman,
  • Muhammad Shahbaz Aslam,
  • Hafiz Muzzammel Rehman,
  • Muhammad Imran Amirzada,
  • Omeeha Nosha,
  • Tayyaba Rehman,
  • Hanan Ahmar,
  • Aizah Amin,
  • Hamid Bashir

摘要

The targeted delivery of anticancer chimeric proteins as a therapeutic agent improves drug effectiveness. Research has concentrated on developing novel treatments by exploiting the properties of cytokines, notably interleukins, to suppress the proliferation of cancerous cells. IL-37 is a cytokine that has anti-inflammatory properties, and it limits the development of hepatocellular carcinoma by impeding cell growth, invasion, and angiogenesis of tumor cells as well as strengthening the body’s immune defenses against cancer while Bombinin (BO1) is a peptide that shows anti-HCC activity by disrupting cell-cycle regulation and inducing apoptosis in liver cancer cells with minimal effects on normal hepatocytes. This study computationally designed a fusion protein IL 37-BO1 by combining the targeting IL-37 with the anti-cancer peptide BO1 via a rigid linker to focus treatment directly on cancerous cells. The secondary structure, tertiary structure, and the physiochemical properties of the engineered fusion protein IL 37-BO1 were estimated through GOR IV, trRosetta, and ProtParam respectively. Validation of protein quality and 3D structure was confirmed using ProSa-web, ERRAT2 and RAMPAGE servers. Next, the IL-37–BO1 fusion protein was docked with the IL18Rα–IL1R8 heterodimer receptor to evaluate its binding characteristics. The docked complex was subsequently analyzed for intermolecular interactions and subjected to molecular dynamics simulation to further investigate its structural stability and dynamic behavior. In-silico study showed that the newly designed possesses a basic composition and a molecular weight of 24 kDa. The ERRAT value of 97.52% and 92.50% of the residues located within the most favorable region were predicted based on SAVES 6.0 analysis, ensuring structural stability. Finally, docking, molecular dynamics simulation, and interaction studies were carried out through ClusPro 2.0, GROMACS and PDBsum and PDBePISA which revealed 20 notable hydrogen bonds and 6 salt bridges, validating the stabilization of the docked complex. Docking and binding affinity analyses revealed a stable interaction, with an MM/GBSA score of − 106.26 kcal/mol and a PRODIGY-predicted binding affinity (ΔG) of − 15.3 kcal/mol. SoluProt also predicted a high expression potential of the fusion protein in E. coli with a score of 0.903. The results indicate that the IL-37-BO1 fusion protein can be expressed effectively in E. coli with high stability and activity. The engineered protein demonstrated reliable performance, effective molecular interaction, and high quality. Overall, the results support IL-37–BO1 as a promising and safe candidate for targeted cancer therapy.